Incorporation of silver salts within a transcutaneous biosensor for infection control

Abstract

The present disclosure provides analyte sensors comprising a sensor tail substrate having a lower portion and configured for insertion into a tissue; a first working electrode disposed on the lower portion of the sensor tail substrate; a first sensing layer disposed upon a surface of the first working electrode; and a membrane disposed over at least the sensing layer; wherein the membrane comprises 20% to 50% by weight of a silver salt. The present disclosure also provides methods of using such analyte sensors for detecting one or more analytes present in a biological sample and methods of manufacturing the analyte sensors.

What is claimed is: 
     
         1 . An analyte sensor comprising:
 a sensor tail substrate having a lower portion and configured for insertion into a tissue;   a first working electrode disposed on the lower portion of the sensor tail substrate;   a sensing layer disposed upon a surface of the first working electrode; and   a membrane disposed over at least the sensing layer;   wherein the membrane comprises 20% to 50% by weight of a silver salt with a particle size of ≤60 μm.   
     
     
         2 . The analyte sensor of  claim 1 , wherein the silver salt is uniformly distributed within the membrane. 
     
     
         3 . The analyte sensor of  claim 1 , wherein the silver salt is selected from the group consisting of silver chloride, silver-silver chloride, silver iodide, and combinations thereof. 
     
     
         4 . The analyte sensor of  claim 1 , wherein the silver salt is silver iodide. 
     
     
         5 . The analyte sensor of  claim 4 , wherein the silver iodide has a particle size of ≤53 μm. 
     
     
         6 . The analyte sensor of  claim 4 , wherein the silver iodide has a purity of at least 99%. 
     
     
         7 . The analyte sensor of  claim 4 , wherein the membrane comprises 30% to 40% by weight of silver iodide. 
     
     
         8 . The analyte sensor of  claim 4 , wherein the membrane comprises 35% by weight of silver iodide. 
     
     
         9 . The analyte sensor of  claim 1 , wherein the analyte sensor does not sensor does not induce cytotoxicity as measured according to ISO 10993-5. 
     
     
         10 . The analyte sensor of  claim 1 , wherein the analyte sensor does not cause skin irritation or skin sensitization according to ISO 10993-10. 
     
     
         11 . The analyte sensor of  claim 1 , wherein the analyte sensor does not cause intradermal irritation according to ISO 10993-10. 
     
     
         12 . The analyte sensor of  claim 1 , wherein the analyte sensor does not cause systemic toxicity according to ISO 10993-11. 
     
     
         13 . The analyte sensor of  claim 1 , wherein the analyte sensor is non-hemolytic according to ISO 10993-4 and ASTM F 756. 
     
     
         14 . The analyte sensor of  claim 1 , wherein the analyte sensor does not cause intramuscular irritation according to ISO 10993-6. 
     
     
         15 . The analyte sensor of  claim 1 , wherein the analyte sensor is not a potential mutagen according to ISO 10993-3 and OECD 471. 
     
     
         16 . A method of inhibiting microorganism growth in an area in and around an insertion site comprising inserting an analyte sensor in a subject in need thereof comprising:
 a first portion positionable above a surface of the skin;   a second portion positionable below the surface of the skin, wherein the second portion is in contact with bodily fluid and configured to measure signals indicative of analyte levels in the bodily fluid;   a first working electrode disposed on the second portion;   a sensing layer disposed upon a surface of the first working electrode; and   a membrane disposed over at least the sensing layer;   wherein the membrane comprises 20% to 50% by weight of a silver salt with a particle size of ≤60 μm, and wherein the analyte sensor does not induce cytotoxicity as measured according to ISO 10993-5.   
     
     
         17 . The method of  claim 16 , wherein the silver salt is silver iodide. 
     
     
         18 . The method of  claim 17 , wherein the silver iodide has a particle size of ≤53 μm. 
     
     
         19 . The method of  claim 17 , wherein the silver iodide has a purity of at least 99%. 
     
     
         20 . A method of preparing an analyte sensor overcoated with a membrane comprising:
 a) mixing a silver salt having a particle size of ≤60 μm and at least one membrane polymer to form a silver salt dispersion, wherein the dispersion comprises 20% to 50% by weight of the silver salt;   b) dipping an analyte sensor into the silver salt dispersion to overcoat the analyte sensor with the silver salt dispersion;   c) curing the analyte sensor; and   d) baking the analyte sensor.   
     
     
         21 . The method of  claim 20 , wherein the silver salt is silver iodide. 
     
     
         22 . An analyte sensor comprising:
 a sensor tail substrate having a lower portion and configured for insertion into a tissue;   a first working electrode disposed on the lower portion of the sensor tail substrate;   a sensing layer disposed upon a surface of the first working electrode;   a membrane disposed over at least the sensing layer; and   a non-electrochemical functional layer comprising a silver salt;   wherein the analyte sensor does not induce cytotoxicity as measured according to ISO 10993-5.   
     
     
         23 . The analyte sensor of  claim 22 , wherein the silver salt is silver iodide with a particle size of ≤60 μm and a purity of at least 99%. 
     
     
         24 . The analyte sensor of  claim 22 , wherein the silver salt is silver-silver chloride.